Conventionally, there have been inventions where a DNA chip is used for determining the gene base sequence (U.S. Pat. No. 5,445,934 and U.S. Pat. No. 5,744,305).
The DNA chip is a plate such as a semiconductor film or a slide glass on which many types of known oligonucleotides are arranged in an array form and fixed to the surface thereof such that the respective minute amounts of suspensions are in dot form. The DNA chip is manufactured such that, in order to form an array of a large number of oligonucleotides on its narrow surface, minute amounts of oligonucleotide suspensions are dispensed at predetermined intervals one by one using a pipette device while avoiding contamination. Various genetic assays and analysis are performed using the DNA chip.
For example, in order to determine an unknown base sequence of a target gene, conventionally, a user dispenses a solution suspended with a target gene substance which is labeled with a luminescent substance, onto the DNA chip. After a predetermined reaction time, excess suspension is removed by washing. Next, by detecting the light emission from the DNA chip, the base sequence is determined from the position where the light emission is detected.
Incidentally, in order to manufacture the DNA chip, if an attempt is made to arrange as many types of oligonucleotides as possible in a narrow area with a high density in a planar form, they come close to each other. As a result, not only is cross contamination easily generated, but also the amounts of the oligonucleotides are further decreased at the respective fixed positions. In particular, if the amounts of the oligonucleotides are decreased at the respective fixed positions, errors easily occur in the determination of the light emitting positions, and there are problems in accuracy.
Moreover, conventionally, there has been used a DNA chip wherein substances such as respective oligonucleotides are fixed on a plane surface such as a glass plate in the form of a prepared slide having a size of about 2.6 cm×7.6 cm. In order to supply a liquid to substances such as the oligonucleotides at the respective fixed positions on the plane surface, a method has been taken wherein, after dispensing about 10 μl of liquid only on the plane surface, a glass plate or a film is manually mounted on the plane surface in a sandwich form, so that a uniform thin liquid layer is formed, and a minute amount of liquid is evenly supplied to the respective fixed positions. In this method, the step for mounting the film or the like has been an obstacle against work automization. Moreover, since the liquid is supplied by mounting the film or the like, it is difficult to fluidize the liquid to be supplied. Furthermore, due to the decrease in the amount, the encountability and the reactivity with the target substance is further decreased, causing a problem in that the process takes time, and a highly dense liquid is required for the process.
Moreover, since the sample is disposed in a planar form, the treatment and the automization become more difficult as the density is increased. Consequently, a very large amount of time and labor is required to manufacture the DNA chip, which increases the price. In particular, in order to analyze, assay, and determine an unknown target substance including a huge amount of base sequences, a large amount of DNA chips are required to be analyzed, assayed, and the like. Therefore, the inventor of the present application has made an invention to solve the problem (International Publication No. WO 01/53831, International Publication No. WO 01/61361, and International Publication No. WO 01/69249), and has disclosed an integrated support having: at least one foundation member formed in a slender shape such as a thread, a cord, a tape, or a rod; and various detection substances fixed in lines in the longitudinal direction of the foundation member having predetermined chemical structures, wherein the foundation member is rolled, laminated, or aligned, and the fixed positions of the various detection substances and the respective chemical structures thereof are associated.
Furthermore, heretofore, as performed by the inventor of the present application, in order to examine the bond of the respective fixed positions and a target substance tagged with a labeling substance, the overall fixed positions or a plurality of fixed positions are measured at once, and the light emission at the respective fixed positions is measured, so as to efficiently examine the chemical structure of the target substance and the affinity thereof (International Publication No. WO 02/063300).
However, even if the manufacture of such an integrated support is easy and the cost is low, there has been a problem in that the advantage of the integrated support is not sufficiently demonstrated unless the reaction, the measurement, and the identification using the integrated support can be efficiently and quickly performed.
On the other hand, if the DNA chip is optically measured, since the DNA chip is a two-dimensional array on a plane surface, in order to measure the light emission at the respective fixed positions, it is necessary to move the light receiving part along a complicated route where the direction and the position are discontinuously changed for the measurement, for example, so as to move it in the Y axis direction while reciprocating along the X axis direction. Therefore, there has been a problem in that the apparatus may be complicated and the scale of the apparatus enlarged.
Moreover, as in the conventional manner, if the presence/absence of a target substance tagged with one type of labeling substance is mainly detected, then regarding a large number of labeled fixed positions, the presence/absence of the labeling substance at the respective fixed positions can be readily identified even if a plurality of fixed positions are measured at once.
However, recently, it is further required to label many types of target substances for determining and analyzing the DNA base sequence. In order to label many types of target substances in this manner, it is not sufficient to merely use a plurality of different types of labeling substances for the respective fixed positions, but it is necessary to specify the quantity ratio (mass ratio) for the labeling (International Publication No. WO 00/5357). At this time, in order to obtain the information from the labeling substances for the respective fixed positions, it has been necessary to obtain detailed information on the respective fixed positions.
Therefore, the present invention has been devised to solve the above problems, with a first object of providing an inexpensive continuous optical measuring apparatus with high cost/performance ratio capable of obtaining the emission of light at respective fixed positions arranged on a foundation member, by a simple device or a control, and a continuous optical measuring method.
A second object is to provide a reliable continuous optical measuring apparatus capable of obtaining the information on the respective fixed positions arranged on the foundation member accurately and precisely, and a continuous optical measuring method.
A third object is to provide a continuous optical measuring apparatus capable of reliably performing the identification in the labeling performed by changing the quantity ratio of a plurality of types of labeling substances generated as a result of reactions at the respective fixed positions on the foundation member, and a continuous optical measuring method.
A fourth object is to provide a continuous optical measuring apparatus capable of consistently and automatically performing the reaction on the foundation member, the measurement, and the identification of the detection substances or the binding substances, and a continuous optical measuring method
A fifth object is to provide a continuous optical measuring apparatus capable of efficiently measuring the light emission at the fixed positions on the foundation member, and a continuous optical measuring method.